Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session II

47-POS Board 47 Dissection of Prion protein and Lipid Interaction

Raiane Santos 2 , Quezia Tedeschi 1 , Jerson Silva 2 , Tuane Vieira 1 . 1 IFRJ, Rio de Janeiro, Brazil, 2 UFRJ, Rio de Janeiro, Brazil.

Introduction: Transmissible spongiform encephalopathies are a group of fatal diseases, which affect mammals, caused by an abnormal isoform of the prion protein (PrP). Conversion of cellular PrP (PrPC) into the pathological conformer, PrPSc, involves contact between both isoforms and probably requires a cellular factor. Recombinant PrP can be converted to an abnormal form via seeded polymerization in vitro techniques in the presence of lipids. Objectives: The importance of lipid molecules for conversion has been revealed, but little is known about the structural features implicit in this interaction. A detailed understanding of this interaction may provide new insights into toxic mechanisms associated with this disease. Material and Methods: In the present work, we used light scattering, FTIR, electron microscopy and fluorescence measurements in order to provide information on the chemical and physical properties of the murine recombinant PrP (rPrP 23-231) interaction with Phosphatidylethanolamine (PE) and Phosfatidic Acid (PA) vesicles. Results and Discussion: We found that phospholipid vesicles raised rPrP light scattering. PE induced changes on PrPC secondary structure, forming soluble oligomers/aggregates with increased β-sheet. PA induced changes on PrPC secondary structure, forming insoluble aggregates. These aggregates were shown to be fibers with increased β-sheet content. Conclusions: Our results suggest that phospholipids, such as PE and PA, play a role in prion aggregation, acting as a cofactor for its pathogenic conformation. On the other hand, these two lipids seem to trigger PrPC aggregation through different pathways, generating different PrPC aggregated forms. These differences may be also important for disease development.

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